NM_001284240.2:c.500A>G

Variant names:

• chr10-84371552-A-G
• rs148835960
• NM_001284240.2:c.500A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001284240.2(CCSER2):​c.500A>G​(p.Asn167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,718 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: CCSER2 NM_001284240.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.335
• Publications: 3 publications found

Genes affected

CCSER2 (HGNC:29197): (coiled-coil serine rich protein 2) Predicted to enable microtubule binding activity. Predicted to act upstream of or within microtubule bundle formation. Predicted to be located in cytoplasm and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036466718).
• BP6: Variant 10-84371552-A-G is Benign according to our data. Variant chr10-84371552-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2216088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284240.2. 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
	CCSER2	NM_001284240.2	MANE Select	c.500A>G	p.Asn167Ser	missense	Exon 2 of 10	NP_001271169.1	Q9H7U1-3
	CCSER2	NM_001351290.2		c.500A>G	p.Asn167Ser	missense	Exon 2 of 12	NP_001338219.1
	CCSER2	NM_001351292.2		c.500A>G	p.Asn167Ser	missense	Exon 2 of 12	NP_001338221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSER2	ENST00000372088.8	TSL:2 MANE Select	c.500A>G	p.Asn167Ser	missense	Exon 2 of 10	ENSP00000361160.2	Q9H7U1-3
	CCSER2	ENST00000359979.8	TSL:1	c.500A>G	p.Asn167Ser	missense	Exon 2 of 3	ENSP00000353068.4	Q9H7U1-2
	CCSER2	ENST00000898573.1		c.500A>G	p.Asn167Ser	missense	Exon 2 of 7	ENSP00000568632.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000355 AC: 89 AN: 250396 AF XY: 0.000362

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00568

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.000231 AC: 337 AN: 1461512 Hom.: 2 Cov.: 32 AF XY: 0.000241 AC XY: 175 AN XY: 727044

African (AFR) AF: 0.000329 AC: 11 AN: 33466

American (AMR) AF: 0.000246 AC: 11 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 138 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.000121 AC: 135 AN: 1111812

Other (OTH) AF: 0.000546 AC: 33 AN: 60388

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74360

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000457 Hom.: 1

Bravo AF: 0.000287

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.036
DANN	Benign	0.24
DEOGEN2	Benign	0.00039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.34
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.026
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.37
MPC		0.063
ClinPred		0.0086	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.094
Mutation Taster		=98/2	polymorphism

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: rs148835960; hg19: chr10-86131308; COSMIC: COSV56503063;