rs2074225

Variant names:

• chr11-61008834-C-T
• rs2074225
• NM_006725.5:c.770C>T
• CD6 p.Ala257Val

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006725.5(CD6):​c.770C>T​(p.Ala257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,545,390 control chromosomes in the GnomAD database, including 258,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A257E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.58 (25911 hom., cov: 34)
  • Exomes 𝑓: 0.57 (233083 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.50
• Publications: 40 publications found

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1915762E-6).
• BP6: Variant 11-61008834-C-T is Benign according to our data. Variant chr11-61008834-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059536.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006725.5. 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
	CD6	NM_006725.5	MANE Select	c.770C>T	p.Ala257Val	missense	Exon 4 of 13	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.770C>T	p.Ala257Val	missense	Exon 4 of 11	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.770C>T	p.Ala257Val	missense	Exon 4 of 11	NP_001241680.1	P30203-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	ENST00000313421.11	TSL:1 MANE Select	c.770C>T	p.Ala257Val	missense	Exon 4 of 13	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.770C>T	p.Ala257Val	missense	Exon 4 of 11	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.770C>T	p.Ala257Val	missense	Exon 4 of 11	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87928 AN: 152034 Hom.: 25897 Cov.: 34

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.535 AC: 103323 AN: 193210 AF XY: 0.541

Gnomad AFR exome AF: 0.641

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.737

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.575 AC: 800477 AN: 1393238 Hom.: 233083 Cov.: 46 AF XY: 0.574 AC XY: 392418 AN XY: 683970

African (AFR) AF: 0.639 AC: 20329 AN: 31832

American (AMR) AF: 0.407 AC: 15306 AN: 37590

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 16083 AN: 21854

East Asian (EAS) AF: 0.426 AC: 16556 AN: 38870

South Asian (SAS) AF: 0.471 AC: 35881 AN: 76110

European-Finnish (FIN) AF: 0.442 AC: 21677 AN: 49064

Middle Eastern (MID) AF: 0.752 AC: 4102 AN: 5458

European-Non Finnish (NFE) AF: 0.593 AC: 637276 AN: 1074994

Other (OTH) AF: 0.579 AC: 33267 AN: 57466

GnomAD4 genome AF: 0.578 AC: 87977 AN: 152152 Hom.: 25911 Cov.: 34 AF XY: 0.568 AC XY: 42229 AN XY: 74376

African (AFR) AF: 0.636 AC: 26415 AN: 41504

American (AMR) AF: 0.498 AC: 7623 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2507 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2217 AN: 5170

South Asian (SAS) AF: 0.466 AC: 2249 AN: 4822

European-Finnish (FIN) AF: 0.431 AC: 4563 AN: 10594

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40079 AN: 67974

Other (OTH) AF: 0.635 AC: 1339 AN: 2110

Alfa AF: 0.592 Hom.: 13431

Bravo AF: 0.592

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.033
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.76
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.5	N
PhyloP100		3.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
PromoterAI		0.028	Neutral
Varity_R		0.042
gMVP		0.46
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2074225;

hg19: chr11-60776306;

COSMIC: COSV57838880;

COSMIC: COSV57838880;