rs2302162

Variant names:

• chr16-89778879-A-G
• rs2302162
• NM_000135.4:c.1777-29T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-89778879-A-G
• chr16-89778879-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000135.4(FANCA):​c.1777-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,613,612 control chromosomes in the GnomAD database, including 5,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (424 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5398 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.329
• Publications: 13 publications found

Genes affected

FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89778879-A-G is Benign according to our data. Variant chr16-89778879-A-G is described in ClinVar as Benign. ClinVar VariationId is 255239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	NM_000135.4	MANE Select	c.1777-29T>C		intron	N/A	NP_000126.2	O15360-1
	FANCA	NM_001286167.3		c.1777-29T>C		intron	N/A	NP_001273096.1	O15360-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.1777-29T>C		intron	N/A	ENSP00000373952.3	O15360-1
	FANCA	ENST00000567205.2	TSL:1	n.1777-29T>C		intron	N/A	ENSP00000457027.2	H3BT53
	FANCA	ENST00000564475.6	TSL:2	c.1777-29T>C		intron	N/A	ENSP00000454977.2	H3BNS0

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9114 AN: 151862 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0546

GnomAD2 exomes AF: 0.0674 AC: 16959 AN: 251460 AF XY: 0.0665

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.0197

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.0585

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.0577

GnomAD4 exome AF: 0.0792 AC: 115813 AN: 1461632 Hom.: 5398 Cov.: 34 AF XY: 0.0777 AC XY: 56486 AN XY: 727132

African (AFR) AF: 0.0113 AC: 378 AN: 33478

American (AMR) AF: 0.0213 AC: 953 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 1491 AN: 26136

East Asian (EAS) AF: 0.165 AC: 6535 AN: 39694

South Asian (SAS) AF: 0.0222 AC: 1912 AN: 86256

European-Finnish (FIN) AF: 0.0573 AC: 3059 AN: 53414

Middle Eastern (MID) AF: 0.0130 AC: 75 AN: 5768

European-Non Finnish (NFE) AF: 0.0867 AC: 96401 AN: 1111772

Other (OTH) AF: 0.0829 AC: 5009 AN: 60390

GnomAD4 genome AF: 0.0600 AC: 9120 AN: 151980 Hom.: 424 Cov.: 32 AF XY: 0.0580 AC XY: 4312 AN XY: 74306

African (AFR) AF: 0.0141 AC: 581 AN: 41332

American (AMR) AF: 0.0379 AC: 579 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5168

South Asian (SAS) AF: 0.0271 AC: 131 AN: 4828

European-Finnish (FIN) AF: 0.0610 AC: 646 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0834 AC: 5670 AN: 68000

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0451 Hom.: 44

Bravo AF: 0.0577

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia complementation group A (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2302162; hg19: chr16-89845287; COSMIC: COSV66880567;