chr2-102718524-G-C

Variant names:

• chr2-102718524-G-C
• rs34977505
• NM_032718.5:c.1321C>G

Variant summary

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

The NM_032718.5(SLC67A2):​c.1321C>G​(p.Pro441Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,613,532 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P441H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (57 hom.)
• Consequence: SLC67A2 NM_032718.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 9.30
• Publications: 2 publications found

Genes affected

SLC67A2 (HGNC:28158): (major facilitator superfamily domain containing 9) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0088353455).
• BP6: Variant 2-102718524-G-C is Benign according to our data. Variant chr2-102718524-G-C is described in ClinVar as Benign. ClinVar VariationId is 775746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032718.5. 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
	SLC67A2	NM_032718.5	MANE Select	c.1321C>G	p.Pro441Ala	missense	Exon 6 of 6	NP_116107.3
	SLC67A2	NM_001322080.2		c.1138C>G	p.Pro380Ala	missense	Exon 6 of 6	NP_001309009.1	B4DKY6
	SLC67A2	NM_001322081.2		c.1138C>G	p.Pro380Ala	missense	Exon 6 of 6	NP_001309010.1	B4DKY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD9	ENST00000258436.10	TSL:1 MANE Select	c.1321C>G	p.Pro441Ala	missense	Exon 6 of 6	ENSP00000258436.5	Q8NBP5
	MFSD9	ENST00000939979.1		c.1318C>G	p.Pro440Ala	missense	Exon 6 of 6	ENSP00000610038.1
	MFSD9	ENST00000962756.1		c.1309C>G	p.Pro437Ala	missense	Exon 6 of 6	ENSP00000632815.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2569 AN: 152160 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00491 AC: 1220 AN: 248506 AF XY: 0.00391

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.00647

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000562

Gnomad OTH exome AF: 0.00417

GnomAD4 exome AF: 0.00209 AC: 3052 AN: 1461254 Hom.: 57 Cov.: 34 AF XY: 0.00194 AC XY: 1410 AN XY: 726924

African (AFR) AF: 0.0585 AC: 1957 AN: 33452

American (AMR) AF: 0.00432 AC: 193 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00637 AC: 166 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86220

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53332

Middle Eastern (MID) AF: 0.00504 AC: 29 AN: 5758

European-Non Finnish (NFE) AF: 0.000354 AC: 394 AN: 1111748

Other (OTH) AF: 0.00500 AC: 302 AN: 60346

GnomAD4 genome AF: 0.0169 AC: 2570 AN: 152278 Hom.: 68 Cov.: 33 AF XY: 0.0165 AC XY: 1226 AN XY: 74450

African (AFR) AF: 0.0572 AC: 2377 AN: 41558

American (AMR) AF: 0.00660 AC: 101 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00234 Hom.: 0

Bravo AF: 0.0198

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0572 AC: 252

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00592 AC: 719

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		9.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.026	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.61
MVP		0.85
MPC		0.25
ClinPred		0.067	T
GERP RS		4.6
Varity_R		0.28
gMVP		0.63
Mutation Taster		=55/45	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: rs34977505; hg19: chr2-103334983;